Observation or LETZ? Is it time to change the consensus guidelines?

Transcription

1 CIN 2-3 in the First Trimester - Observation or LETZ? Is it time to change the consensus guidelines? Dr Efraim Siegler Carmel Medical Center Chairman The Israeli Society of Colposcopy and Cervical & Vulvar Pathology NO Conflict of interests

2 CARMEL Medical Center CIN Arch Gyn Obs (2013) 287; / Population based study of 8.8 million births in Canada CANCER CX 3.3/ % of Cervical Cancer occurred in pregnant Women McIntyre Seltman Obs Gyn Clin North Am:2008:35:

3 CIN 2-3 Management Women with high-grade CIN require treatment; observational follow-up is not an option! Cytopathology 2009,20,5-16

4 Why are we treating CIN 2-3? 1. Diagnose Cervical Cancer 2. Prevent Cervical Cancer

5 Why are we treating CIN 2-3? Cervical Cancer is found in some 2% of women with HSIL ( on PAP Test ), risk rises with age, and is low in years women Jones BA & al: Arch Pathol Lab Med 2000;124; CX Cancer is found in 5.4% of women with HSIL on PAP Test +HPV HR +. Katcki HA & al :JLGTD 2013;Vol 17;Issue 5, S50-S55

6 Why are we treating CIN 2-3? Invasive carcinoma diagnosed in excisional specimens of women treated because CIN 2-3 lesions Up to 7% if unsatisfactory colposcopy Duddan BD et al : AJOG 1999;180(2) % ( 1683 LLETZ operations because CIN 2-3 ) Siegler E, Bornstein J; LLETZ in Israel ; Gynecologic And Obstetric Investigation 2011; Vol. 72 (2), pp. 85-9

7 Preventing Cervical Cancer During the years Dr. Green didn't treat patients with CIN 3 Mc Credie M & al The Lancet Oncology, Volume 9, Issue 5, Pages , May 2008 Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study In 143 women managed only by punch or wedge biopsy, cumulative incidence of invasive cancer of the cervix or vaginal vault was 31 3% (95% CI ) at 30 years, and 50 3% ( ) in the subset of 92 such women who had persistent disease within 24 months. However, cancer risk at 30 years was only 0 7% ( ) in 593 women whose initial treatment was deemed adequate or probably adequate, and whose treatment for recurrent disease was conventional.

8 Schiffman M,Rodriguez AC. Heterogeneineity in CIN 3 diagnosis Lancet Oncology 2008:9: CIN 3 20% of CIN 3 progress to Invasive Carcinoma within 5 years 80% 5 30

9 GUIDELINES OF CIN TREATMENTS in PREGNANCY

10 Guidelines of CIN TREATMENTS in PREGNANCY Journal of Lower Genital Tract Disease Vol 11 No 4,2007, Obs & Gyn Vol 112, No 6 Dec 2008 p Cytopathology 2009,20,5-16 Massad LS & al JLGTD Supplement April 2013 S1-S27

11 ACOG Management of Abnormal Pap & CIN in pregnancy( 2008 ) TREAT ONLY IF INVASION IS SUSPECTED Why delay Treatment? 1.CIN 2-3 doesn't progress to Invasion! 2.The treatment is very dangerous! (Abortions,severe bleeding, premature delivery ) Hunter M. & al ; CIN in Pregnancy AMJOG July 2008 ;Vol 3-9

12 CIN Lesions during Pregnancy : % Regress / Disappear 25-47% Persist 3%-30% Progress! Palle C et al : April 2000 Acta Obst Gynec Scand79;306-10;2000 Vlahos G et al : Gyn Obstet Invest 2002;54;78-81 Yost NP et al ;Obs Gyn 93; ;1999 Douviers et al :Gynecol Obs fertility 31; ;2003. Fader AN,&al; AJOG 2010;203;113e1-6 The risk of CIN 2-3 to progress to Invasive Carcinoma?

13 CIN 2-3 In pregnancy Regression- Persistence Progression to Carcinoma - Name No Age Dig REGRES % PERSIS % PROGRES No(%) Fader : AJOG HSIL Yost : Ob& Gyn CIN Wetta LA : JLGT HSIL 0 Cubo Abert :JLGTD < HSIL

14 CARMEL Medical Center Carcinoma Cervix U S Surveillance Epidemiology and End Results ( SEER ) Nov 2010;Nat Cancer Inst 2011 Cervical Cancer Incidence in women : Younger than 20 years was 0.05/100,000 women Women at years was 15/100,

15 NO CIN 2-3 in Pregnancy - Progression to Carcinoma OVER 25 years old Name No Pat Mean Age Dig Regres s (%) Persist (%) Progress (%) 1 Copolla A :Gyn Onc :67: ( 1997) CIS 88 2(8%) 2 Giraud: J Gynecol Obstet Biol Reprod (Paris). 1997; 16 CIN 3 3(18%) 3 Pale C : Acta Obs Gyn Scandina 2000 Apr ;79;(4) CIN (2%) 4 Mitsushasi A ; Int J Obst & Gyn 71(2000) ( 22.2%) 5 Vlahos G :Gy Ob Inves 2002 :54: CIN Kaplan K :Cancer Cytopathology 2004:102; HSIL 100 3(10.7%) 7 Robova H :Eur J Gynaecol Oncol. 2005;26(6): (9.7%) 8 Ackerman S ::Acta Obstet Gynecol Scand. 2006;85(9): CIS 34% 63.1% 2(2.6%) 9 Frega A:Anticancer Research 27: (2007) CIN (4.7%) 10 Serati M:Acta Obstet Gynecol Scand. 2008;87(12): CIN Cubo-Abert M :JLGTD 16(1) Jan 2012 ( Over 25 years ) 33 >25 HSIL (6.1%) 12 Coppolilo: Acta Obst Gyn Scan 2013:92; CIN % 70% 4( 13.3%) 13 Schaefr K : Int J Gynaecol Obstet Aug;118(2): CIN (11%) 14 Karrberg C : Acta Obstet Gynecol Scand Jun;92(6): CIN 3 3(7.1%) 15 Siegler E : J Low Gen Tract Disease Vol 18 No : CIN (12.9%) 608 ( (6.0%) 6.1%)

16 NO CIN 2-3 in Pregnancy - Progression to Carcinoma OVER 25 years old Name No Pat Mean Age Dig Regres s (%) Persist (%) Progress (%) 1 Copolla A :Gyn Onc :67: ( 1997) CIS 88 2(8%) 2 Giraud: J Gynecol Obstet Biol Reprod (Paris). 1997;26(5): CIN 3 3(18%) 3 Pale C : Acta Obs Gyn Scandina 2000 Apr ;79;(4) CIN (2%) 4 Mitsushasi A ; Int J Obst & Gyn 71(2000) ( 22.2%) 5 Vlahos G :Gy Ob Inves Women 2002 :54:78-81 over years 28 CIN Kaplan K :Cancer Cytopathology 2004:102; HSIL 100 3(10.7%) 7 Robova H :Eur J Gynaecol Oncol. 2005;26(6): (9.7%) 8 Ackerman S ::Acta Obstet Gynecol Scand. 2006;85(9): ???? CIS 34% 63.1% 2(2.6%) 9 1 Frega A:Anticancer Research 27: (2007) CIN (4.7%) 10 Serati M:Acta Obstet Gynecol Scand. 2008;87(12): with CIN 2-3 lesions had a risk of 6.1 % to progress to Invasive Carcinoma CIN Cubo-Abert M :JLGTD 16(1) Jan 2012 ( Over 25 years ) 33 >25 HSIL (6.1%) 12 Coppolilo: Acta Obst Gyn Scan 2013:92; ? CIN % 70% 4( 13.3%) 13 Schaefr K : Int J Gynaecol Obstet Aug;118(2): CIN (11%) 14 Karrberg C : Acta Obstet Gynecol Scand Jun;92(6): CIN 3 3(7.1%) 15 Siegler E : J Low Gen Tract Disease Vol 18 No : CIN (12.9%) 608 ( (6.0%) 6.1%)

17 Discovery consists of looking at the same thing as everyone else and thinking something different Albert Szent-Györgyi Nobel Prize 1937 Vit C discovery

18 Why are the wrong recommendations? Mixing different grade of CIN in one article. Mixing different ages in one article. Mixing complications of LLETZ treatments during all the trimesters of pregnancy in one article. Old articles ( Knife Cone ) % of CIN 2-3 doesn't progress to Invasive Cancer in one year!(5-10% will progress to invasion )

19 Yost : Ob& Gy Mean age: 24 years Copolla A :Gyn Onc 1997 :67: (8%) Cancer The gestational age range of those : patients who had significant morbidity was weeks Robinson January 1997 Vol 64,

20 Morice P,Uzan C,Gouy S The Lancet Volume 379, Issue 9815,Pages 558-9,

21 CIN 2-3 diagnosed during pregnancy Partial data from ISRAEL registry Siegler E (1, 4), Vaknin Z (2, 5) Amit A (3, 4), Lavie O (1, 4), Mackuli L (1), Auslender R (1, 4), Weissman A (2, 4)and The Israeli Colposcopy Group- Department of Obstetrics and Gynecology, Carmel Medical Center (1), Assaf Harofe Medical Center (2),Rambam Medical Center (3), Rappoport Faculty of Medicine, Technion Insitute of Technology (4), Haifa, Israel, Sackler Faculty of Medicine, Tel Aviv University (5), Tel Aviv, Israel 76 women were diagnosed with CIN 2-3 Average age 32.5 years Final pathological results are known in 74 women Cervical Cancer 5 women 6. 8% CIN 2-3/ AIS 56 women 75.7% CIN 1 4 women 5.4% Normal 9 women 12.2% Total 74 women 100%

22 CIN 2-3 during PREGNANCY OBSERVATION Group 36 women were followed during pregnancy Average age - years 32.4 In 34 women the final pathological result is known : INVASIVE CARCINOMA 2 women ( 5.8% ) CIN 2-3 : 22 women (64.7% ) CIN 1 / Normal 10 women ( 29.4% ) Total 1 Women still pregnant 1 Women lost to follow up. 34 women Doctors recommendation Women preference.

23 CIN 2-3 during PREGNANCY LLETZ Treatment Group-( I Trimester) 40 women underwent LLETZ till 14 weeks Average age - years 32.5 * 1 women =18 weeks INVASIVE CARCINOMA : 3 women (7.5 %) CIN 2-3 /AIS : 34 women (85%) CIN 1- Normal Histology : 3 women ( 7.5% ) Total 40 women (100%)

24 CIN 2-3 during PREGNANCY LLETZ Treatment Group-( I Trimester) 40 women underwent LLETZ till 14 weeks ANESTHESIA : 32 operations General anesthesia: 8 operations local anesthesia. Complications : No women suffered massive / severe bleeding. 2 women were treated because minor bleeding 1 women Cervical suture at 22 w / Delivery 37 weeks

25 CIN 2-3 during PREGNANCY LLETZ Treatment Group-( I Trimester) 40 women underwent LLETZ till 14 weeks 7 women underwent LLETZ and D +C 4 women - Missed Abortion before LLETZ. 3 women - Termination of Pregnancy. 33 women continued their pregnancy 23 women - ( 69.7 %) Term delivery 2 women - ( 6.1 %) Late preterm delivery (34,34 W) 7 women - ( 21.2%) Ongoing III Trimester 1 women - ( 3%) Ongoing II Trimester

26 Our Experience with 40 LLETZ during the first trimester * Diagnose Invasive Cancer in 7.5% of the women. No case of severe bleeding/ abortion. Most of delivery Term or Late pre term. No case of recurrence after delivery.

27 CIN 2-3 diagnosed during pregnancy Partial data from ISRAEL Observation LLETZ Treatment Total CANCER 2 (5.8%) 3(7.5%) 5(6.8%) CIN 2-3/AIS 22 ( 64.7%) 34(85%) 56 (75.7%) CIN 1/ NORMAL 10 (29.4%) 3(7.5%) 13(17.5%) TOTAL (Final Pathology) ONGOING/ LOST 2 TOTAL

28 N o Author (year) Invasive Ca./ MIC Term deliveries 1 Dunn (100%) 2 Hannigan 13 b? 7 c ( 100%) 1982 ( Knife Cone ) 3 Robinson (100%) 4 Penna -1998( Laser) 8 8 8(100%) 5 Fambrini (2007) (Laser) Mitsuhashi (100%) 7 Frega a 4 1 5(100%) 8 Schaefer (88%) 2 Late Preter 9 Siegler (82?%) ( This study -Not Published ) LLETZ /LASER CONE till 16 weeks I st Trimes Cin LLETZ III TOTAL (8.5% ) 2= 34,34,w

29 Science is the father of knowledge, but opinion breeds ignorance. Hippocrates BC For too many years the treatment of pregnant women is based on opinions, Its it time for guidelines and decisions based on science

30 Also DURING PREGNANCY LLETZ during the first trimester appears to be a safe François-Auguste-René Rodin procedure with few complications. The benefit of diagnosing Cervical Cancer in 6-10% of the women should be considered against the risk of complications. In each women a personalized treatment should be selected according to the pathological results, the colposcopic image,the HPV type? the risk factors of the women and the patient preference.

31 Williams Obstetrics 16 Th Edition * ALSO DURING PREGNANCY Muller CY :Obs Gyn Clin N Am 32(2005) Dunn TS ; Gyn Oncol 90(2003)

32 BAHAI GARDENS HAIFA

33 TEL HASOMER CIN SIEGLER